Diols are valuable intermediates in the preparation of polymers, acetals, and crown ethers, and optically active diols, in particular, have been widely used for stereochemical control in homochiral syntheses. Unfortunately, the number of optically active diols, other than those associated with carbohydrates is quite small. Thus, a general source of optically active diols could provide valuable new building blocks for many structures.
Most techniques for the preparation of optically active diols focus on the stereospecific synthesis of a single enantiomer. The chemicals for preparing both enantiomers via such a procedure are not always available. In addition, in many cases, the stereochemistry at the second chiral center is determined by that at the first, limiting the allowable distance between the two. Finally, a completely different approach is generally required for preparing the meso stereoisomer.
An efficient method for the preparation of all possible stereoisomers of symmetric, secondary diol monomers would allow, for example, the synthesis of an all (R), an all (S) or an (R,S) "pseudo-syndiotactic" polymer as well as polymers containing any combination of the above stereochemistries. While the separation of stereoisomers can be achieved by vapor phase chromatography (VPC) (Koppenhoefer, B.; Walswer, M.; Bayer, E.; Abdalla, S., J. Chromatog., 1986, 358, 159), such a method is, strictly speaking, not useful on a preparative scale.
Hydrolase enzymes specific for diol stereochemistry have been exploited for some time. However, their use has been limited to the modification of one chiral center in a meso diol (or diacetylated meso diol) (Hemmerle, H., Gais, H. J, Tetrahedron Lett., 1987, 28, 3471), or to the modification of a specific hydroxyl (or esterified hydroxyl) of a diol bearing a prochiral center (Ramos Tombo, G. M.; Schar, H. P.; Fernandez i Busquets, X.; Ghisalba, O., Tetrahedron Lett., 1986, 27, 5707).
Early examples of using enzymes to hydrolyze one of a pair of like groups involved the stereoselective hydrolysis of one of a pair of esters in aqueous media (Huang, F. C.; Lee, L. F. H.; Mittal, R. S. D.; Ravikumar, P. R.; Chan, J. A.; Sih, C. J.; Caspi, E.; Eck, E. R., J. Am. Chem. Soc., 1975, 97, 4144; Ohno, M.; Kobayashi, S.; Limori, T.; Wang, Y. F.; Izawa, T., J. Am. Chem. Soc., 1981, 103, 2405; Chen, C. S.; Fujimoto, Y.; Sih, C. J., J. Am. Chem. Soc., 1981, 103, 3580). The recent discovery, however, (Cambou, B,; Klibanov, A. M., J. Am Chem. Soc., 1984, 106, 2687; Zaks, A.; Klibanov, A. M., Science, 1984, 224, 1249; Gatfield, I. L., Annals N.Y. Acad. Sci., 1984, 568; Zaks, A.; Klibanov, A. M., Proc. Natl. Acad. Sci U.S.A., 1985, 82, 3192; Klibanov, A. M., CHEMTECH, 1986, 354) that such enzymes are also effective catalysts in low to moderate polarity organic solvents has allowed the development of esterification and transesterification as viable, alternative processes, enzymes can carry out (Cambou, B.; Klibanov, A. M., Biotechnology and Bioengineering, 1984, XXVI, 1449; Kirchner, G.; Scollar, M. P.; Klibanov, A. M., J. Am. Chem. Soc., 1985, 107, 7072; Langrand, G.; Secchi, M.; Buono, G.; Baratti, J.; Triantaphylides, C., Tetrahedron Lett., 1985, 26, 1857; Langrand, G.; Baratti, J.; Buono G.; Triantaphylides, C., Tetrahedron Lett., 1986, 27, 29; Gil, G.; Ferre, F.; Meou, A.; Le Petit, J.; Triantaphylides, C., Tetrahedron Lett., 1987, 28, 1647; Bianchi, D.; Cesti, P.; Battistel, E., J. Org. Chem., 1988, 53, 5531; F.; Cesti, P.; Cabri, W.; Bianchi, D.; Martinengo, T.; Foa, J. Org. Chem., 1987, 52, 5079).
In a typical organic phase resolution, the enzyme catalyzes the reaction of an activated ester with one enantiomer of a racemic alcohol. When the reaction has reached approximately 50% completion, it is stopped by filtering out the enzyme catalyst. The products of interest are an unchanged, optically active alcohol and an optically active ester. Following separation of the unchanged alcohol enantiomer from the ester, the latter can be hydrolyzed (chemically or enzymatically) to obtain the second enantiomer of the optically active alcohol.
In a modification of this procedure, Bianchi et al. have shown that acid anhydrides can be used with lipases in place of the activated ester to stereoselectively esterify chiral alcohols (Bianchi, D.; Cesti, P.; Battistel, E., J. Org. Chem., 1988, 53, 5531). This method exhibits both high reaction rates and selectivities.
Because of the current interest in the preparation of optically active polymers, and due to a lack of feasible large-scale methods for the preparation of isolated stereoisomeric AA type monomers, there is still a need for simple, large-scale methods for the preparation of secondary diol monomers which result in high purity, stereochemically pure isomers which are substantially free of the remaining stereoisomers of the compound.